| 1. |
- Bondesson, Maria, et al.
(författare)
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A CASCADE of effects of bisphenol A.
- 2009
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:4, s. 563-7
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Damdimopoulou, Pauliina, et al.
(författare)
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A single dose of enterolactone activates estrogen signaling and regulates expression of circadian clock genes in mice.
- 2011
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Ingår i: The Journal of nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 141:9, s. 1583-9
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Tidskriftsartikel (refereegranskat)abstract
- Enterolactone (EL) is an enterolignan produced by gut microbiota from dietary plant lignans. Epidemiological and experimental studies suggest that EL and plant lignans may reduce the risk of breast and prostate cancer as well as cardiovascular disease. These effects are thought to at least in part involve modulation of estrogen receptor activity. Surprisingly little is known about the in vivo estrogenicity of EL. In the present study, we investigated the target tissues of EL, the genes affected by EL treatment, and the response kinetics. Following a single dose of EL, luciferase was significantly induced in reproductive and nonreproductive tissues of male and female 3xERE-luciferase mice, indicating estrogen-like activity. Microarray analysis revealed that EL regulated the expression of only 1% of 17β-estradiol target genes in the uterus. The majority of these genes were traditional estrogen target genes, but also members of the circadian signaling pathway were affected. Kinetic analyses showed that EL undergoes rapid phase II metabolism and is efficiently excreted. In vivo imaging demonstrated that the estrogen response followed similar, fast kinetics. We conclude that EL activates estrogen signaling in both male and female mice and that the transient responses may be due to the fast metabolism of the compound. Lastly, EL may represent a link among diet, gut microbiota, and circadian signaling.
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| 3. |
- Pongratz, Ingemar
(författare)
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Regulation of dioxin receptor activity by phosphorylation and protein-protein interaction
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dioxin receptor together with its partner factor Arnt belongs to the basic helix-loop-helix/PAS family of transcription factors. The receptor is the mediator of the biological effects of a number of environmental pollutants such as dioxin and other related compounds. At the molecular level the dioxin receptor has been shown to, in the presence of agonists to the receptor, activate a battery of genes involved in metabolic activation and clearing of xenobiotic compounds from the cell. In the absence of ligand the dioxin receptor is present in the cytosolic compartment of the cell coupled to a dimer of the molecular chaperone hsp90. In the presence of ligand the dioxin receptor is found in the nuclear compartment of the cell as a heterodimeric form with its partner factor Arnt. This heterodimer interacts with xenobiotic responsive elements (XRE) in the vicinity of dioxin inducible genes to activate transcription. We have studied the activation mechanisms of the dioxin receptor. We show that the molecular chaperone hsp90 is required to maintain the dioxin receptor in a ligand binding conformation as well to inhibit an otherwise constitutive DNA binding activity. This DNA binding activity is critically dependent on dimerization with Arnt and appears to be regulated by a protein kinase C-dependent mechanism. In addition we have performed a detailed analysis of the determinants of dimerization and DNA binding activity of the dioxin receptor. We describe a critical role of the PAS domain in determining a dimerization specificity: it restricts an otherwise broad dimerization activity of the DNA binding basic helix-loop-helix domain.
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| 4. |
- Spichtinger, Daniel, et al.
(författare)
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Key issues in European food science research: a review of the European Food Science Day 2009
- 2010
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Ingår i: Quality Assurance and Safety of Crops & Foods. - 1757-8361. ; 2:3, s. 114-119
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Forskningsöversikt (refereegranskat)abstract
- This paper is a report on the European Food Science Day (Brussels, 18 November 2009, organized by the CommNet network of food science communicators) and its outcomes. The article presents FP 7 as a key funding mechanism in European food and nutrition research and it puts research in this sector in a socio-economic context. The article then reviews the specific activities of several EU-funded projects in the field of risk, safety, and health, discussing key issues and research questions in these fields.
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